Direct-Acting Antivirals (Hepatitis C & B)

Introduction & scope

• Direct-acting antivirals (DAAs) — small-molecule oral drugs that directly target specific HCV non-structural (NS) proteins essential for replication — unlike the indirect/immunomodulatory action of interferons.
• Term usage — "DAA" is used almost exclusively for HCV; HBV is treated with nucleoside/nucleotide analogues ± pegIFN-α which act directly on HBV polymerase but are not conventionally called DAAs. This topic covers both.
• Two paradigms — HCV — positive-sense RNA flavivirus, cytoplasmic replication, does not integrate or establish latency, and is curable (cure = sustained virologic response, SVR). HBV — partially dsDNA hepadnavirus forming nuclear cccDNA that no current drug eliminates, so cure is not possible; treatment suppresses replication lifelong.
• Vaccine & cure asymmetry — HBV is vaccine-preventable but not curable; HCV has no vaccine (extreme genetic heterogeneity) but is curable.
• Hepatitis A and E (faecal-oral, self-limiting) have no antiviral therapy; hepatitis D (defective, needs HBV) has limited options (pegIFN-α, bulevirtide).